PROJECT SUMMARY This proposal is for the purchase of a Becton Dickenson (BD) FACSAria Fusion cell sorter in an integrated biosafety cabinet for placement in the UMass Medical School (UMMS) Flow Cytometry Research Core Facility that serves over 120 principal investigators each year, 70 of whom currently rely on cell sorting. The Flow Core currently utilizes four BD FACSAria IIs cell sorters that are all between 10 and 15 years old, all of which will become obsolete in 2022 when the manufacturer discontinues parts and service support for all Aria II instruments. Our researchers that depend on these instruments come from 14 different departments and over 90% of them are NIH-funded. These investigators have helped to make UMMS a world-leader in translational research, coupling basic biomedical research to a bench-to-bedside innovation engine. UMMS researchers have made pivotal advances in HIV, cancer, diabetes, autoimmunity, infectious disease and in understanding the molecular basis of disease. Cell sorting has been central to many of these advances. Our current, heaviest cell sorting usage comes from the new UMMS RNA Therapeutics Institute. The RTI is dedicated to leveraging the strong RNA biology and clinical research communities at UMMS to develop novel therapies for which RNA is the therapeutic target or modality. Several other Major Users come from the UMMS Diabetes Center of Excellence that brings together diabetes investigators with a focus on human biology, including the cellular processes that contribute to insulin-producing cell dysfunction, autoimmunity, pancreatic ?-cell proliferation, and potential prevention and reversion strategies. As our current sorters are booked to capacity two weeks in advance, these investigators in particular struggle for timely access to cell sorting because this research depends on precious, unique patient material that can arrive unpredictably. The 5-laser BD Fusion will be an essential first step in the update of our Core Instrumentation and its addition will also greatly increase access to sorting for our users, as we will continue using our older sorters as long as possible, until additional new cell sorters are acquired. The UMMS Research Advisory Committee has endorsed in principle a plan to replace three of our aging cell sorters over the next 3 years. Recognizing that institutional funds are limiting, this proposal for a Shared Instrumentation Grant is an essential part of that plan, as our need to replace three cell sorters in a short time far exceeds the available UMMS equipment replacement budget. The new BD Fusion with UV laser and increased sensitivity for small particle detection will not only replace the outdated equipment but will also improve the sensitivity, resolution, and reproducibility of our sorting capabilities. As our 3 most- used sorters will become obsolete when service and parts become unavailable in 2022, we cannot wait for them to begin failing before we purchase replacements. This BD FACSAria Fusion will be the first step in ensuring that the UMMS Flow Core can provide timely, reliable, state-of-the-art cell sorting for our dynamic, growing pool of NIH-funded researchers.